Rituximab, Chemotherapy, and Filgrastim in Treating Patients With Burkitt's Lymphoma or Burkitt's Leukemia

NCT ID: NCT00039130

Last Updated: 2023-08-21

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

105 participants

Study Classification

INTERVENTIONAL

Study Start Date

2002-05-31

Study Completion Date

2014-10-31

Brief Summary

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RATIONALE: Monoclonal antibodies such as rituximab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Colony-stimulating factors such as filgrastim may increase the numbers of immune cells found in bone marrow or peripheral blood and may help a person's immune system recover from the side effects of chemotherapy. Combining chemotherapy with rituximab and filgrastim may kill more cancer cells.

PURPOSE: Phase II trial to study the effectiveness of combining rituximab with chemotherapy and filgrastim in treating patients who have Burkitt's lymphoma or Burkitt's leukemia.

Detailed Description

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OBJECTIVES:

* Determine the complete response rate in patients with previously untreated Burkitt's lymphoma or Burkitt's leukemia treated with rituximab and high-intensity chemotherapy with filgrastim (G-CSF) support.
* Determine the progression-free and overall survival of patients treated with this regimen.
* Determine the feasibility and toxicity of this regimen in these patients.

OUTLINE: This is a multicenter study. Patients are stratified according to disease (leukemia vs lymphoma).

* Course 1: Patients receive cyclophosphamide IV over 5-15 minutes daily on days 1-5 and oral prednisone on days 1-7. Allopurinol PO will be given on days 1-14.
* Courses 2, 4, and 6: Patients receive ifosfamide IV over 1 hour daily on days 1-5; vincristine IV over 10 minutes and methotrexate IV over 24 hours on day 1; leucovorin calcium IV over 15 minutes every 6 hours on day 2; cytarabine IV over 2 hours on days 4 and 5 and etoposide IV over 1 hour daily on days 4 and 5; oral dexamethasone daily on days 1-5; and methotrexate and cytarabine intrathecally (IT) on day 1. During course 2, patients receive rituximab IV over 1-4 hours on days 8, 10, and 12. During courses 4 and 6, patients receive rituximab IV over 1 hour on day 8. Patients also receive filgrastim (G-CSF) subcutaneously (SC) beginning on day 7 and continuing until blood counts recover.
* Courses 3, 5, and 7: Patients receive cyclophosphamide IV over 5-15 minutes daily on days 1-5; vincristine IV over 10 minutes and methotrexate IV over 24 hours on day 1; leucovorin calcium IV every 6 hours on day 2; doxorubicin IV daily on days 4 and 5; oral dexamethasone daily on days 1-5; methotrexate and cytarabine IT on day 1; and rituximab IV over 1 hour on day 8. Patients also receive G-CSF as in courses 2, 4, and 6. After course 3, treatment continues in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually for 5 years.

PROJECTED ACCRUAL: A total of 100 patients (50 per stratum) will be accrued for this study within 3 years.

Conditions

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Leukemia Lymphoma

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Rituximab with High Intensity Chemotherapy

Cycle1: Cyclophosphamide 100 mg/m\^2/day (d) IV (d 1-5), Prednisone 60 mg/m\^2/d oral (d 1-7), Allopurinal 300 mg/d oral (d 1-14) Cycle 2, 4 \& 6 (21 day): Ifosfamide 800 mg/m\^2/d (d 1-5), Dexamethasone 10 mg/m\^2/d (d1-5), Methotrexate 150 mg/m\^2 load, then 1.35 g/m\^2 over 23.5 h (d 1), Leucovorin 25 mg/m\^2 36 h after methotrexate (d 2) then 10 mg/m\^2 every 6 h, Vincristine 2 mg push (d 1), Cytarabine 1000 mg/m\^2/d over 2 h (d 4-5), Etoposide 80 mg/m\^2.d over 1 h (d 4-5), Filgrastim 5 mg/kg/d (d 7-21 as needed), Rituximab 50 mg/m\^2 d 8 cycle 2 only, 375 mg/m\^2/d (d 10, 12 cycle 2, d 8 cycle 4 \& 6) Cycle 3, 5 \& 7 (21 day): Cyclophosphamide 200 mg/m\^2/day (d) IV (d 1-5), Dexamethasone 10 mg/m\^2/d (d1-5), Methotrexate 150 mg/m\^2 load, then 1.35 g/m\^2 over 23.5 h (d 1), Leucovorin 50 mg/m\^2 36 h after methotrexate (d 2) then 10 mg/m\^2 every 6 h, Vincristine 2 mg push (d 1), Doxorubicin 25 mg/m\^2/d (d 4-5), Filgrastim 5 mg/kg/d (d 7-21 as needed), Rituximab 375 mg/m\^2/d (d 8)

Group Type EXPERIMENTAL

filgrastim

Intervention Type BIOLOGICAL

5 ug/kg/day sub Q injection day 7 until ANC\>5000/ul courses II-VII

rituximab

Intervention Type BIOLOGICAL

Day 8 course II 50 mg/sq m IV infusion: d 8 course IV \& VI 375mg/sq m IV Day 10 course II: 325 mg/sq m IV infusion Day 12 course II: 375 mg/sq m IV infusion

cyclophosphamide

Intervention Type DRUG

200 mg/sq m/day IV infusion over 5-15 min days 1-5, courses I, III, V, VII

cytarabine

Intervention Type DRUG

1 g/sq m/day IV infusion Days 4 \& 5, courses II, IV, VI

dexamethasone

Intervention Type DRUG

10mg/sq m PO or IV Days 1-5 courses II-VII

doxorubicin hydrochloride

Intervention Type DRUG

25 mg/sq m/day IV infusion Days 4 \& 5 courses III,V, VII

etoposide

Intervention Type DRUG

80 mg/sq m/day IV infusion Days 4 \& 5 courses II, IV, VI

ifosfamide

Intervention Type DRUG

800 mg/sq m/day IV infusion Days 1-5 courses II, IV, VI

leucovorin calcium

Intervention Type DRUG

25mg/sq m IV infusion over 15 min then 10 mg IV q 6 hrs until serum MTX \<10nM, courses II-VII

methotrexate

Intervention Type DRUG

1.5 g/sq m IV infusion Day 1 courses II-VII

prednisone

Intervention Type DRUG

60 mg/sq m PO/day Days 1-7 course I

vincristine sulfate

Intervention Type DRUG

2 mg IV push Day 1 courses II-VII

Allopurinol

Intervention Type DRUG

300 mg/day PO Days 1-14, course I

Interventions

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filgrastim

5 ug/kg/day sub Q injection day 7 until ANC\>5000/ul courses II-VII

Intervention Type BIOLOGICAL

rituximab

Day 8 course II 50 mg/sq m IV infusion: d 8 course IV \& VI 375mg/sq m IV Day 10 course II: 325 mg/sq m IV infusion Day 12 course II: 375 mg/sq m IV infusion

Intervention Type BIOLOGICAL

cyclophosphamide

200 mg/sq m/day IV infusion over 5-15 min days 1-5, courses I, III, V, VII

Intervention Type DRUG

cytarabine

1 g/sq m/day IV infusion Days 4 \& 5, courses II, IV, VI

Intervention Type DRUG

dexamethasone

10mg/sq m PO or IV Days 1-5 courses II-VII

Intervention Type DRUG

doxorubicin hydrochloride

25 mg/sq m/day IV infusion Days 4 \& 5 courses III,V, VII

Intervention Type DRUG

etoposide

80 mg/sq m/day IV infusion Days 4 \& 5 courses II, IV, VI

Intervention Type DRUG

ifosfamide

800 mg/sq m/day IV infusion Days 1-5 courses II, IV, VI

Intervention Type DRUG

leucovorin calcium

25mg/sq m IV infusion over 15 min then 10 mg IV q 6 hrs until serum MTX \<10nM, courses II-VII

Intervention Type DRUG

methotrexate

1.5 g/sq m IV infusion Day 1 courses II-VII

Intervention Type DRUG

prednisone

60 mg/sq m PO/day Days 1-7 course I

Intervention Type DRUG

vincristine sulfate

2 mg IV push Day 1 courses II-VII

Intervention Type DRUG

Allopurinol

300 mg/day PO Days 1-14, course I

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

DISEASE CHARACTERISTICS:

* Histologically, cytogenetically, or immunophenotypically confirmed Burkitt's leukemia or Burkitt's or Burkitt-like lymphoma

* L3 morphology surface IgG expression
* Cytogenetic evidence for t(8;14), t(8;22), or t(2;8)
* Previously untreated disease except hydroxyurea for leukocytosis
* CNS involvement allowed
* Patients with Burkitt's leukemia or Burkitt's lymphoma with bone marrow involvement must also be enrolled on CALGB-8461
* Patients with Burkitt's leukemia must also be enrolled on CALGB-9665

PATIENT CHARACTERISTICS:

Age:

* 16 and over

Hepatic:

* Bilirubin no greater than 1.5 times upper limit of normal (ULN)

Renal:

* Creatinine no greater than 1.5 times ULN

Other:

* HIV negative
* Not pregnant or nursing
* Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

* No concurrent interleukin-11

Chemotherapy:

* See Disease Characteristics
* No other concurrent chemotherapy

Endocrine therapy:

* No concurrent hormonal therapy except for non-disease-related conditions (e.g., insulin for diabetes)
* No concurrent steroids except for adrenal failure

Radiotherapy:

* No concurrent palliative radiotherapy except whole-brain irradiation for documented CNS disease
Minimum Eligible Age

16 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

Alliance for Clinical Trials in Oncology

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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David Rizzieri, MD

Role: STUDY_CHAIR

Duke University Medical Center Bone Marrow Transplant

Locations

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Naval Medical Center - San Diego

San Diego, California, United States

Site Status

Tunnell Cancer Center at Beebe Medical Center

Lewes, Delaware, United States

Site Status

CCOP - Christiana Care Health Services

Newark, Delaware, United States

Site Status

Walter Reed Army Medical Center

Washington D.C., District of Columbia, United States

Site Status

University of Illinois Cancer Center

Chicago, Illinois, United States

Site Status

University of Chicago Cancer Research Center

Chicago, Illinois, United States

Site Status

Fort Wayne Medical Oncology and Hematology

Fort Wayne, Indiana, United States

Site Status

Hematology Oncology Associates of the Quad Cities

Bettendorf, Iowa, United States

Site Status

Holden Comprehensive Cancer Center at University of Iowa

Iowa City, Iowa, United States

Site Status

Greenebaum Cancer Center at University of Maryland Medical Center

Baltimore, Maryland, United States

Site Status

Union Hospital Cancer Program at Union Hospital

Elkton, Maryland, United States

Site Status

Masonic Cancer Center at University of Minnesota

Minneapolis, Minnesota, United States

Site Status

Ellis Fischel Cancer Center at University of Missouri - Columbia

Columbia, Missouri, United States

Site Status

Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center

Lebanon, New Hampshire, United States

Site Status

Cancer Institute of New Jersey at Cooper - Voorhees

Voorhees Township, New Jersey, United States

Site Status

Roswell Park Cancer Institute

Buffalo, New York, United States

Site Status

Monter Cancer Center of the North Shore-LIJ Health System

Lake Success, New York, United States

Site Status

CCOP - North Shore University Hospital

Manhasset, New York, United States

Site Status

Don Monti Comprehensive Cancer Center at North Shore University Hospital

Manhasset, New York, United States

Site Status

Long Island Jewish Medical Center

New Hyde Park, New York, United States

Site Status

Stony Brook University Cancer Center

Stony Brook, New York, United States

Site Status

Presbyterian Cancer Center at Presbyterian Hospital

Charlotte, North Carolina, United States

Site Status

Duke Comprehensive Cancer Center

Durham, North Carolina, United States

Site Status

Wayne Memorial Hospital, Incorporated

Goldsboro, North Carolina, United States

Site Status

Wake Forest University Comprehensive Cancer Center

Winston-Salem, North Carolina, United States

Site Status

Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center

Columbus, Ohio, United States

Site Status

Rhode Island Hospital Comprehensive Cancer Center

Providence, Rhode Island, United States

Site Status

Miriam Hospital

Providence, Rhode Island, United States

Site Status

Mountainview Medical

Berlin Corners, Vermont, United States

Site Status

Fletcher Allen Health Care - University Health Center Campus

Burlington, Vermont, United States

Site Status

Virginia Commonwealth University Massey Cancer Center

Richmond, Virginia, United States

Site Status

Countries

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United States

References

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Rizzieri DA, Johnson JL, Byrd JC, Lozanski G, Blum KA, Powell BL, Shea TC, Nattam S, Hoke E, Cheson BD, Larson RA; Alliance for Clinical Trials In Oncology (ACTION). Improved efficacy using rituximab and brief duration, high intensity chemotherapy with filgrastim support for Burkitt or aggressive lymphomas: cancer and Leukemia Group B study 10 002. Br J Haematol. 2014 Apr;165(1):102-11. doi: 10.1111/bjh.12736. Epub 2014 Jan 15.

Reference Type RESULT
PMID: 24428673 (View on PubMed)

Other Identifiers

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U10CA031946

Identifier Type: NIH

Identifier Source: secondary_id

View Link

CALGB-10002

Identifier Type: -

Identifier Source: secondary_id

CDR0000069354

Identifier Type: REGISTRY

Identifier Source: secondary_id

CALGB-10002

Identifier Type: -

Identifier Source: org_study_id

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